麻黄碱对脑缺氧缺血后新生大鼠神经可塑性影响的研究

目的：研究麻黄碱对新生大鼠缺氧缺血性脑损伤(HIBD)后神经可塑性的影响。方法：7日龄SD大鼠60只,制成HIBD模型,随机分为麻黄碱组(1.5 mg·kg^-1)、D-苯丙胺(D-AMPH,1.0 mg·kg^-1)组、三磷酸胞苷二钠(CTP,70 mg·kg^-1)组、神经节苷脂(GM1,20 mg·kg^-1)组和自然康复组。用免疫组织化学方法检测海马CA₃区生长相关蛋白-43(GAP-43)、突触素(SYP)表达的变化,术后4周进行5 d的Morris水迷宫学习和记忆的测试。结果：①麻黄碱组海马CA₃区GAP-43和SYP表达水平高于自然康复组(P＜0.05),与D-AMPH,CTP组的表达无显著性差异；②各组平均逃避潜伏期明显短于自然康复组(P＜0.05),原平台穿过次数各组明显多于自然康复组(P＜0.01)。麻黄碱组逃避潜伏期长于GM1组,原平台穿过次数麻黄碱组少于GM1组,但与CTP和D-AMPH组比无差异。结论：麻黄碱能提高新生HIBD大鼠年长后的空间定向能力和学习记忆能力。这种保护作用和麻黄碱减少HIBD后神经元的丢失、促进参与神经元重塑的蛋白分子GAP-43和SYP的表达有关。麻黄碱对HIBD的保护作用和D-AMPH及CTP起同样的效果,而改善新生HIBD大鼠年长后的空间定向能力和学习记忆能力的效果稍差于GM1,这可能和麻黄碱的剂量有关。

Effect of ephedrine on neuronal plasticity in neonatal rats after hypoxic-ischemic brain injury

OBJECTIVE: To study the effect of ephedrine on neural plasticity after hypoxic-ischemic brain damage (HIBD) in neonatal rats. METHOD: Sixty SD rats, aged 7 days, were made as HIBD model, which were randomly divided into following 4 groups, an ephedrine group, a D-amphetamine (D-AMPH) group, a cytodine triphosphate-2Na (CTP) group and a ganglioside (GMI) group. Changes in the expression of growth-associated protein-43 (GAP-43) and synaptophysin (SYP) in the hippocampal area CA3 were detected with immunohistochemical method. Four weeks after the operation, learning and memory test in Morris water maze was performed for 5 days. RESULT: (1) The GAP-43 and SYP expression levels in hippocampal area CA3 in the ephedrine group were higher than those in the spontaneous recovery group (P < 0.05), with no significantly different from those the CTP group and the D-AMPH group. (2) The average escape latency in the ephedrine group, the D-AMPH group and the CTP group were significantly shorter than that in the spontaneous recovery group (P < 0.05), and the frequency passing the original platform in the 3 treatment groups were significantly more than those in the spontaneous recovery group (P < 0.01). The escape latency was longer and the frequency passing the original platform was less in the ephedrine group than that in the GM1 group, with no significant differences as compared with the CTP group and the D-AMPH group. CONCLUSION: Ephedrine can enhance spatial orientation and learning and memory abilities of HIBD rats in later life. This protective effect is associated with decrease of neuronal loss after HIBD, and promotion of the expression of GAP43 and SYP. Ephedrine can exert the same protection against HIBD as D-AMPH and CTP do, but the amelioration of spatial orientation and learning and memory abilities by ephedrine in later life in rats after HIBD is slightly weaker than that by GM1, which is possibly related with the dose of ephedrine.